Probing the formation, structure and free energy relationships of M protein dimers of SARS-CoV-2

Computational and Structural Biotechnology Journal

Xiangfei Meng¹  Rui Yang²  Zhiyong Yuan³  Wei Wang⁴  Imshik Lee⁵  Chengwen Yang⁵  Ningbo Liu⁵  Hongji Dai⁵  Shengpeng Jiang⁵  Yipeng Cao⁵ 

[1] College of Physics, Nankai University, Tianjin 300071, PR China;National Supercomputer Center in Tianjin, 300457 PR China;Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology of Tianjin, PR China;Department of Infection and Immunity, Tianjin Union Medical Center, Nankai University Affiliated Hospital. 300031, PR China;Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060 PR China;

关键词: COVID-19;    SARS-CoV-2;    Coronavirus;    Membrane (M) protein;    Free energy calculations;    MMPBSA;   

DOI  :  

来源: DOAJ

【 摘 要 】

The M protein of the novel coronavirus 2019 (SARS-CoV-2) is the major structural component of the viral envelope and is also the minimum requirement for virus particle budding. M proteins generally exist as dimers. In virus assembly, they are the main driving force for envelope formation through lateral interactions and interactions with other viral structural proteins that play a central role. We built 100 candidate models and finally analyzed the six most convincing structural features of the SARS-CoV-2 M protein dimer based on long-timescale molecular dynamics (MD) simulations, multiple free energy analyses (potential mean force (PMF) and molecular mechanics Poisson-Boltzmann surface area (MMPBSA)) and principal component analysis (PCA) to obtain the most reasonable structure. The dimer stability was found to depend on the Leu-Ile zipper motif and aromatic amino acids in the transmembrane domain (TMD). Furthermore, the C-terminal domain (CTD) effects were relatively small. These results highlight a model in which there is sufficient binding affinity between the TMDs of M proteins to form dimers through the residues at the interface of the three transmembrane helices (TMHs). This study aims to help find more effective inhibitors of SARS-CoV-2 M dimers and to develop vaccines based on structural information.

【 授权许可】

Unknown